Diverse roles and modulations of I_A in spinal cord pain circuits

This review highlights recent findings of different amplitude ranges, roles, and modulations of A-type K⁺ currents (I_A) in excitatory (GAD67-GFP^-) and inhibitory (GAD67-GFP⁺) interneurons in mouse spinal cord pain pathways. Endogenous neuropeptides, such as TAFA4, oxytocin, and dynorphin in particular, have been reported to modulate I_A in these pain pathways, but only TAFA4 has been shown to fully reverse the opposing modulations that occur selectively in LIIo GAD67-GFP^- and LIIi GAD67-GFP⁺ interneurons following both neuropathic and inflammatory pain. If, as hypothesized here, Kv4 subunits underlie I_A in both GAD67-GFP^- and GAD67-GFP⁺ interneurons, then I_A diversity in spinal cord pain pathways may depend on the interneuron-subtype-selective expression of Kv4 auxiliary subunits with functionally different N-terminal variants. Thus, I_A emerges as a good candidate for explaining the mechanisms underlying injury-induced mechanical hypersensitivity.